7-fluoro-N-(2-fluorophenyl)-3-oxo-1,2,3,5-tetrahydropyrido[1,2-a]benzimidazole-4-carboxamide -Drug Synthesis Database

【结构式】

【分子编号】22297

【品名】7-fluoro-N-(2-fluorophenyl)-3-oxo-1,2,3,5-tetrahydropyrido[1,2-a]benzimidazole-4-carboxamide

【CA登记号】

【分子式】C₁₈H₁₃F₂N₃O₂

【分子量】341.3170464

【元素组成】C 63.34% H 3.84% F 11.13% N 12.31% O 9.38%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(X)

Michael addition of acrylonitrile (II) to 4-fluoro-2-nitroaniline (I) in the presence of Triton B provided nitrile (III). The nitro group of (III) was then reduced to the amine (IV) by hydrogenation over Pd/C. Further cyclization of amine (IV) with ethyl (ethoxycarbonyl)acetimidate (V) furnished the benzimidazole (VI). Diester (VII) (prepared by refluxing the nitrile (VI) with ethanolic HCl), was submitted to Dieckmann cyclization in the presence of NaOEt to produce the pyridobenzimidazole (VIII). Reaction of the ester group of (VIII) with 2-fluoroaniline (IX) in boiling xylene yielded the corresponding anilide (X), which was finally alkylated with ethoxymethyl chloride (XI) in the presence of NaH and crown ether.

参考文献中间体

合成目标

【1】 Sanfilippo, P.J.; Reitz, A.B.; Kordik, C.P.; Dubinsky, B.; Rosenthal, D.I.; Vaidya, A.H.; Jordan, A.D.; Wu, W.-N.; Potential anxiolytic agents. Part 4: Novel orally-active N(5)-substituted pyrido[1,2-a]benzimidazoles with high GABA-A receptor affinity. Bioorg Med Chem Lett 2002, 12, 17, 2381.
【2】 Cohen, J.H.; et al.; Process research for the synthesis of RWJ-51204, a novel anxiolytic agent. Org Process Res Dev 1999, 3, 4, 260.
【3】 Reitz, A.B.; Jordan, A.D.; Sanfilippo, P.J.; Scott, M.K. (Ortho-McNeil Pharmaceutical, Inc.); 5-Heteroatom-containing alkyl substd.-3-oxo-pyrido(1,2-a)benzimidazole-4-carboxamide derivs. useful in treating central nervous system disorders. EP 0935598; US 5817668; WO 9815553 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	22288	4-fluoro-2-nitrophenylamine; 4-fluoro-2-nitroaniline	364-78-3	C₆H₅FN₂O₂	详情	详情
(III)	22290	3-(4-fluoro-2-nitroanilino)propanenitrile		C₉H₈FN₃O₂	详情	详情
(IV)	22291	3-(2-amino-4-fluoroanilino)propanenitrile		C₉H₁₀FN₃	详情	详情
(VI)	22293	ethyl 2-[1-(2-cyanoethyl)-5-fluoro-1H-benzimidazol-2-yl]acetate		C₁₄H₁₄FN₃O₂	详情	详情
(VII)	22294	ethyl 3-[2-(2-ethoxy-2-oxoethyl)-5-fluoro-1H-benzimidazol-1-yl]propanoate		C₁₆H₁₉FN₂O₄	详情	详情
(VIII)	22295	ethyl 7-fluoro-3-oxo-1,2,3,5-tetrahydropyrido[1,2-a]benzimidazole-4-carboxylate		C₁₄H₁₃FN₂O₃	详情	详情
(IX)	22296	2-fluorophenylamine; 2-fluoroaniline	348-54-9	C₆H₆FN	详情	详情
(X)	22297	7-fluoro-N-(2-fluorophenyl)-3-oxo-1,2,3,5-tetrahydropyrido[1,2-a]benzimidazole-4-carboxamide		C₁₈H₁₃F₂N₃O₂	详情	详情

Extended Information